The research conducted under this grant will examine the forms of experimental obesity. The first of these occurs in rodents where it is transmitted as an autosomal recessive trait (fatty rat; obese mouse; diabetes mouse). The other form of obesity is produced by hypothalamic injury. In the genetically transmitted form of obesity, the proposal under study is that there is a single biochemical lesion which is responsible for the myriad of effects observed in these animals. This hypothesis is based on the one gene one enzyme hypothesis originally formulated by Beadle and Tatum. The studies in hypothalamic obese rats will deal with the role of the autonomic nervous system in the pathogenesis of this syndrome. Both the vagus and sympathetic nervous system have been implicated in this syndrome and these implications will be explored in detail.